3，4-亚甲基二氧基甲基苯丙胺对大鼠的神经毒性及维生素C的保护作用  

Neurotoxicity of 3,4-methylenedioxymethamphetamine and protection with vitamin C in rats

作　　者：王志云[1] 肖玉芳[2] 李素霞[3] 

机构地区：[1]邯郸市妇幼保健院药械科,邯郸056001 [2]河北工程学院临床医学院妇科,邯郸056002 [3]北京大学中国药物依赖性研究所,北京100083

出　　处：《中国新药杂志》2008年第11期942-946,共5页Chinese Journal of New Drugs

摘　　要：目的:探讨3,4-亚甲基二氧基甲基苯丙胺(MDMA)的神经毒性机制及抗氧化剂维生素C是否具有MDMA神经毒性的保护作用。方法:雄性Wistar大鼠随机分为正常对照组、MDMA组、MDMA给药前30 min给予维生素C组、MDMA给药后3 h给予维生素C组、MDMA给药后5 h给予维生素C组,MDMA和维生素C均为单剂量腹腔注射,剂量分别为20和250 mg·kg^(-1)。1周后采用高效液相色谱法测定海马、枕叶皮层5-羟色胺(5-HT)的含量,原位杂交方法检测SERTmRNA,免疫组织化学法检测GFAP蛋白。结果:与正常对照组比较,MDMA组大鼠枕叶皮层、海马5-HT含量均明显下降(P<0.05),大鼠海马SERTmRNA的表达明显下降(P<0.05),而脑组织GFAP蛋白的表达显著升高(P<0.05)。与MDMA组比较,提前30 min和MDMA后3 h给予维生素C两组的5-HT含量和海马SERTmRNA的表达无明显改变(P>0.05),而给予MDMA后5 h给予维生素C组的5-HT含量和海马SERTmRNA的表达明显增加(P<0.05);不同时间给予维生素C的3组大鼠脑组织GFAP蛋白的表达均较MDMA组显著降低(P<0.05)。结论:MDMA对中枢5- HT系统具有明显的神经毒性;在给予MDMA后5 h给予维生素C对5-HT能系统有保护作用。Objective ：To explore the mechanism of neurotoxicity of 3,4-methylenedioxymethamphetamine （MDMA） and the protection with antioxidant vitamin C （VitC）. Methods：Male Wistar rats were randomly assigned to normal control group,MDMA group,MDMA ＋ VitC（ -30 min） group, MDMA ＋ VitC（3 h） group and MDMA ＋ VitC（5 h） group,the latter 4 groups were intraperitoneally treated with single dose of MDMA 20 mg.kg -1 ,and the latter 3 groups were administered intraperitoneally single dose of VitC 250 mg. kg -1 30 min before,3 h and 5 h after MDMA administration, respectively. On the 7th day post-treatment of MDMA, 5-HT in hippocampus and occipital cortex ware measured by high performance liquid chromatography; the expression of SERTmRNA was detected by in situ hybridization; and the expression of protein GFAP was detected by immunohistochemistry. Results： Compared with control group, MDMA group had a significantly decreased concentration of 5-HT in rat hippocampus and occipital cortex （P 〈 0.05） , a significantly decreased expression of SERTmRNA in hippocampus and a significantly increased expression of GFAP in brain tissue （P 〈 0.05 ）. The administration of VitC 30 min before and 3 h after MDMA did not attenuate the decrease of 5-HT and the expression of SERTmRNA, while VitC administered 5 h after MDMA inhibited the decrease of functional markers of 5-HT. As to the expression of GFAP, VitC treated at three time points down regulates GFAP expression. Conclusion：MDMA could cause neurotoxicity to 5-HT system. VitC treated 5 h after MDMA could afford neuroprotection to 5-HT system.

关 键 词：3 4-亚甲基二氧基甲基苯丙胺(MDMA) 神经毒性 维生素C 神经保护 

分 类 号：R965.1[医药卫生—药理学] R971.7[医药卫生—药学]